Angiopoietins contribute to lung development by regulating pulmonary vascular network formation

Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its e...

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Veröffentlicht in:Biochemical and biophysical research communications 2009-04, Vol.381 (2), p.218-223
Hauptverfasser: Hato, Tai, Kimura, Yoshishige, Morisada, Tohru, Koh, Gou Young, Miyata, Keishi, Tabata, Mitsuhisa, Kadomatsu, Tsuyoshi, Endo, Motoyoshi, Urano, Takashi, Arai, Fumio, Araki, Kimi, Suda, Toshio, Kobayashi, Koichi, Oike, Yuichi
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container_issue 2
container_start_page 218
container_title Biochemical and biophysical research communications
container_volume 381
creator Hato, Tai
Kimura, Yoshishige
Morisada, Tohru
Koh, Gou Young
Miyata, Keishi
Tabata, Mitsuhisa
Kadomatsu, Tsuyoshi
Endo, Motoyoshi
Urano, Takashi
Arai, Fumio
Araki, Kimi
Suda, Toshio
Kobayashi, Koichi
Oike, Yuichi
description Angiopoietin (Ang) signaling through the Tie2 receptor regulates vasculature. The role of Ang signaling in pulmonary hypertension is well investigated, but its role in lung development is not elucidated. Here, we show that the Tie2 agonist ligand, Ang1, was detected in lung tissue at birth and its expression gradually increased in mice, whereas its antagonist Ang2 was abundant at birth and decreased inversely with Ang1. Mice expressing the potent chimeric Ang1 protein COMP-Ang1 in surfactant protein C (SPC)-positive lung epithelial cells, showed 50% lethality at birth due to respiratory failure. Surviving mice displayed impaired adaptive responsive respiratory function. Histological analysis revealed that pulmonary artery and alveolar structure were significantly dilated, and alveolar density was decreased to approximately a third of controls. Thus, the precise regulation of Tie2 signaling through an Ang1/Ang2 expression switch is important to construct a mature lung vascular network system required for normal lung development.
doi_str_mv 10.1016/j.bbrc.2009.02.030
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subjects Angiogenesis
Angiopoietin-1
Angiopoietin-1 - genetics
Angiopoietin-1 - metabolism
Angiopoietin-2 - genetics
Angiopoietin-2 - metabolism
Animals
Bronchopulmonary dysplasia (BPD)
Bronchopulmonary Dysplasia - genetics
Cell Differentiation - genetics
Humans
Infant, Newborn
Lung - abnormalities
Lung - blood supply
Lung - growth & development
Lung development
Mice
Mice, Transgenic
Neovascularization, Physiologic - genetics
Receptor, TIE-2 - metabolism
Recombinant Fusion Proteins - genetics
Vasodilation - genetics
title Angiopoietins contribute to lung development by regulating pulmonary vascular network formation
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